The principal purpose of this trial is to assess the potential for treatment with the essential trace element selenium (Se) to prevent prostate cancer (PCa). The rationale for this trial is based on the results of the Nutritional Prevention of Cancer Trial, a randomized, double-blind clinical intervention trial. The results of this trial show a 63 percent reduction in PCa incidence during the initial 10 years of follow up in the patients receiving 200 mug/d of Se compared to the placebo group1. The trial will randomize patients to either placebo or one of two Se dosages, 200 mug/d or 400 mug/d The primary endpoints for the trial are the incidence of PCa and the velocity of the primary serum marker of prostate cancer progression, prostate specific antigen (PSA). Safety endpoints for the trial include onset of early mild symptoms of Se toxicity as well as significant changes in liver and kidney enzyme levels. The trial will randomize at least 700 patients with persistently elevated PSA levels (greater than 4 ng/ml) and at least one negative biopsy for prostate cancer. The trial will follow patients for up to 57 months, (an average of 51 months) and have 80 percent power to detect a 50 percent decrease in the incidence of PCa with an alpha of 0.05. The treatment effect of 50 percent was selected because it is one half the treatment effect observed in the NPC trial after a two year treatment lag (RR=0.25). In addition to PCa incidence, prostate biopsies and surgical tissue will be analyzed to explore both biomarkers of prostate cancer progression and possible mechanisms by which Se supplementation affects PCa.